The long range objective of this project is to identify the role of one of the major effector cell types of non-adaptive immunity, the natural killer (NK) cells, in the general mechanisms of resistance of the organism. The working hypothesis derived from our research and that of others is that a) human NK cells represent a relatively homogenous discrete cell type, with various defensive and regulatory activities including, but not limited to cell mediated cytotoxicity; b) NK cells effectiveness and specificity in vivo depends on a complex network of interaction with humoral factors and other cellular types that can be effectively analyzed in in vitro experiments; c) some of the regulatory and functional mechanisms of NK cells, as well as surface molecules, are similar but not necessarily identical to those of cytotoxic T cells and of myelomonocytic cells. In order to analyze this hypothesis and to further our understanding of the lineage, function, and regulation of human NK cells we propose to continue the characterization of the surface phenotype of human NK cells, to analyze the ability of NK cells to produce lymphokines, to investigate the role of surface interactions and secretion in the mechanism of cytotoxicity, to study activation and growth of NK cells, and to characterize NK precursor cells.